Experimental meningitis by Streptococcus pneumoniae and Neisseria meningitidis in rodents

Bacterial meningitis (BM) is a global public health issue that affects patients of all ages. The two leading causes of BM worldwide are Streptococcus pneumoniae (the pneumococcus) and Neisseria meningitidis (the meningococcus). Despite the use of antibiotics and vaccines, both pneumococcal meningitis (PM) and meningococcal meningitis (MM) result in high case fatality rates and long-term neurological sequelae. Moreover, increasing resistance to first-line antibiotics, limited vaccine coverage, serotype replacement in vaccinated population, and lack of adjunctive therapies to control brain damage are all matters of concern in the management of PM and MM. The availability of animal models of PM and MM is crucial to characterize the pathogenetic and pathophysiologic mechanisms of disease as well as to identify novel antimicrobial agents, adjuvant therapies and vaccine candidates. Historically, animal models of BM employed large animals to mimic the disease in humans, such as monkeys for MM and rabbits for PM. However, since the introduction of rodents, both rats and mice have demonstrated to be robust, reliable, and suitable species for modeling both PM and MM. Depending on the route of infection, the dose of bacterial inoculum, the animal age and strain, different experimental readouts are obtained that permit to answer specific scientific questions. This chapter describes the main features of two models of PM and MM developed in the infant rat and adult mouse, respectively. Each model system presents unique characteristics that allow to study different aspects of the disease. The broad range of different forms of brain injury that can be observed in the PM infant rat model enables to study the entire spectrum of the pathophysiology of brain damage in PM and allows to evaluate novel therapeutic strategies and their impact on long-term neurological sequelae. The MM mouse model is suitable to investigate the role of meningococcal virulence factors in the disease, the host–parasite interactions in the central nervous system, and the efficacy of drugs to control the infection and limit brain damage in MM.